Water → HCID 135998255, compound

HRID 1809189Notes

Reaction equation

HRID 1809189 reaction equation
Br[C:2]1[N:6]2[C:7]([CH3:23])=[CH:8][N:9]=[C:10]([NH:11][CH2:12][C:13]3[CH:18]=[CH:17][C:16]([S:19]([NH2:22])(=[O:21])=[O:20])=[CH:15][CH:14]=3)[C:5]2=[N:4][CH:3]=1.CC1(C)C(C)(C)OB([C:32]2[CH:37]=[CH:36][C:35]([OH:38])=[CH:34][CH:33]=2)O1.C([O-])([O-])=O.[K+].[K+].O.O(C1C=CC=CC=1P(C1C=CC=CC=1)C1C=CC=CC=1)C1C=CC=CC=1P(C1C=CC=CC=1)C1C=CC=CC=1>CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[OH:38][C:35]1[CH:36]=[CH:37][C:32]([C:2]2[N:6]3[C:7]([CH3:23])=[CH:8][N:9]=[C:10]([NH:11][CH2:12][C:13]4[CH:18]=[CH:17][C:16]([S:19]([NH2:22])(=[O:21])=[O:20])=[CH:15][CH:14]=4)[C:5]3=[N:4][CH:3]=2)=[CH:33][CH:34]=1

Participants

8

Reactant 5

HCID 962WaterHCID 11430Potassium CarbonateHCID 27346244-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenolHCID 4285986Bis[2-(diphenylphosphino)phenyl] etherHCID 58337113HCID 58337113, compound

Product 1

HCID 135998255HCID 135998255, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
88 °C

Procedure

A mixture of 4-[(3-Bromo-5-methyl-imidazo[1,2-a]pyrazin-8-ylamino)-methyl]-benzenesulfonamide (0.1 g, 0.252 mmol), 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenol (0.061 g, 0.277 mmol), K2CO3 1.5M in water (0.34 mL, 0.504 mmol), Pd(OAc)2 (3.0 mg, 0.013 mmol), and (oxidi-2,1-phenylene)bis(diphenylphosphine) (14 mg, 0.026 mmol) in DMF 1 mL is stirred at 88° C. overnight. The reaction mixture is filtered through cotton, diluted with AcOEt, washed with water, the organic layer dried with MgSO4 anh. filtered and evaporated. The crude mixture is purified by prep. HPLC under acid conditions using a gradient of 0.1% formic acid in H2O/0.1% formic acid in Acetonitrile (95/5:5 min, 9/1:13 min, 0/1:4 min) to give 4-{[3-(4-hydroxy-phenyl)-5-methyl-imidazo[1,2-a]pyrazin-8-ylamino]-methyl}-benzenesulfonamide as a brown oil, (36.5 mg) LC-MS m/z 410 [M+H]+.

Workup

  1. filtrationThe reaction mixture is filtered through cotton
  2. additiondiluted with AcOEt
  3. washwashed with water
  4. dry with materialthe organic layer dried with MgSO4 anh. filtered
  5. customevaporated
  6. customThe crude mixture is purified by prep
  7. customa gradient of 0.1% formic acid in H2O/0.1% formic acid in Acetonitrile (95/5:5 min, 9/1:13 min, 0/1:4 min)

Sources & evidence

ORD record
ord-88e8c2b4dc014d4996ba1b2a72b3c34f
Source dataset
uspto-grants-2013_01
Patent number
US08362018B2

Reaction notes

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